Thursday, June 20, 2013

Signalling in intrinsically disordered proteins

I take a small interest in biology and biophysics because of its complexity and the large number of unsolved but important problems. Lately I've noticed an increase in the number of popular articles on intrinsically disordered proteins (IDP's). These proteins are shaking up conventional wisdom on how proteins work and the importance of their structures.

This interesting News & Views article in Nature summarizes some recent work on disordered proteins and how they respond to activators and inhibitors. While I don't understand much of the jargon in the article, the overall message is exciting. I found the following excerpts of interest:

The observation of striking differences in the crystal structures of haemoglobin in the presence and absence of oxygen seemed to validate the idea that allostery [the link is my own] can be rationalized, and possibly even quantitatively accounted for, by examining the structural distortions that connect the different oxygen-binding sites... This structural view of allostery has largely guided the field ever since. However, the realization that more than 30% of the proteome — the complete set of proteins found in a cell — consists of intrinsically disordered proteins (IDPs), and that intrinsic disorder is hyper-abundant in allosteric signalling proteins such as transcription factors, raises the possibility that a well-defined structure is neither necessary nor sufficient for signal transmission.
The take-home message of Ferreon and colleagues' work, and the reason that a switch is possible, is that proteins should not be thought of as multiple copies of identical structures that respond uniformly to a signal. Instead, proteins — especially IDPs — exist as ensembles of sometimes radically different structural states. This structural heterogeneity can produce ensembles that are functionally 'pluripotent', a property that endows IDPs with a unique repertoire of regulatory strategies.

I absolutely love that IDP's are currently rewriting the dogmas of much of molecular biology.